1. Field of the Invention
The present invention relates to a method for the production of 5-cyclohexylmethylhydantoin derivatives which are useful as starting materials for the production of drugs, and to 5-(3-cyclohexene-1-yl)methylenehydantoin derivatives which are intermediates for the production of such 5-cyclohexylmethylhydantoin derivatives.
2. Discussion of the Background
2-Amino-3-cyclohexylpropionic acid (.beta.-cyclohexylalanine) is a compound whose importance as a constituent of drugs has been increasing in recent years (J. R. Luly, et al., J. Med. Chem., vol. 31, p.2264 (1988)). Many methods for the synthesis of .beta.-cyclohexylalanine are known, and one of the potent synthetic methods is a method involving the hydrolysis of 5-cyclohexylmethylhydantoin (A. Kleemann, et al., Japanese Patent Application Disclosure SHO 57-150645; Kaneko, et al., Amino Acid Industry, 5-7 Kodansha, 1973).
5-Cyclohexylmethylhydantoin may be obtained by the reduction of 5-cyclohexylmethylenehydantoin, and the methods which are known for the production of 5-cyclohexylmethylenehydantoin include (A) a method in which 5-cyclohexylmethylenehydantoin is obtained by the reaction of phosphonyl hydantoin obtained by the bromination of hydantoin at the 5-position followed by phosphonation thereof by a Michaelis-Arbuzov reaction, with cyclohexane carbaldehyde (N. A. Meanwell, et al., J. Org. Chem., vol. 56, p.6897 (1991)), and is then reduced; and (B) a method in which cyclohexane carbaldehyde is condensed directly with hydantoin. However, there are problems with Method (A), because it involves many steps, and also because cyclohexane carbaldehyde is costly. In addition, Method (B) has the same disadvantage of using the costly cyclohexane carbaldehyde, and therefore neither method can be said to be industrially useful.
Thus, there remains a need for a simple, safe, and low-cost method for the production of 5-cyclohexylmethylhydantoin and derivatives thereof. There also remains a need for intermediates useful in such a method for the production of 5-cyclohexylmethylhydantoin and derivatives thereof.